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Biomedical subjects

R C Holman

Publications and source records attributed to R C Holman.

At least 91 records · Page 5Linked to original sources

Survival analysis of hemophilia-associated AIDS cases in the US.

Using national hemophilia-associated AIDS (acquired immunodeficiency syndrome) surveillance data and the life table method of survival analysis, the median length of survival of hemophilic patients in the United States after the diagnosis of AIDS was 11.7 months; the cumulative probability of survival at one year was 49.2 +/- 2.0 percent; at two years, 28.9 +/- 2.3 percent. Patients 13-29 years of age at the time of diagnosis had the longest survival and those 60 years and older had the shortest. Patients diagnosed since 1986 survived longer than those diagnosed before 1986. Length of survival did not differ significantly by race, coagulation disorder, AIDS manifestation at the time of diagnosis, or region of residence. Seven patients survived more than 36 months after AIDS was diagnosed. These patients were similar to those surviving for a shorter duration except that they were more likely to have met only the 1987 revision of the Centers for Disease Control AIDS surveillance case definition (as opposed to the 1985 case definition). Results of this study suggest that survival among hemophilic patients after the diagnosis of AIDS is similar to that reported by other investigators for other AIDS risk groups, excluding patients with Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

Necrotizing enterocolitis mortality in the United States, 1979-85.

The Multiple Cause of Death Mortality data from the National Center for Health Statistics were analyzed to describe epidemiologic characteristics and trends in deaths related to necrotizing enterocolitis (NEC) among infants in the United States from 1979 to 1985. The average annual mortality rate (multiple cause mortality) for NEC was 13.1 deaths per 100,000 live births. NEC annual mortality rates decreased significantly during the study period for White and Black infants, male and female infants, and infants in the Northeast, North Central, and South regions. Black infants were approximately three times more likely to die from NEC than White infants, and the NEC infant mortality rate was highest in the South.

Black or African American↗

HIV and hemophilic children's growth.

The acquired immune deficiency syndrome (AIDS) often has profound effects on growth; however, the effects of human immunodeficiency virus (HIV) on asymptomatic children's growth are unknown. Before heat inactivation/HIV donor screening of factor concentrates, many hemophilic children became infected with HIV. We evaluated four hemophilic groups without AIDS, using age-standardized growth parameters: group 1, 41 HIV-seropositive children (median age of 13 years); group 2, 11 HIV-seronegative children (median age of 4 years); group 3, 20 children frequently receiving concentrates, evaluated before 1979 (median age of 9 years); and group 4, 11 children rarely receiving concentrates, evaluated before 1979 (median age of 6 years). Median height for age (HA), weight for age (WA), and weight for height (WH) of groups 1 and 2 exceeded the 50th percentile of referent norms. HA, WA, WH, and weight/height did not vary significantly by group, nor did these decline over periods of 11 to 70 months. However, for those less than 11 years of age in group 1, HA declined by 25 percentile points over at least a 3 year period. Also, group 1's T helper-to-suppressor cell ratios at 12 +/- 3 months following the latest growth evaluation were positively associated with both HA and WA at the last evaluation. Eight children were evaluated before 1979 and again after they seroconverted to HIV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Comparison of methods for assessing chemotaxis of monocytes and polymorphonuclear leukocytes isolated from patients with AIDS or AIDS-related conditions.

We evaluated the ability of normal human peripheral blood monocytes and polymorphonuclear leucocytes (PMNL) isolated from patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related conditions (ARC) to migrate toward a chemoattractant. Migration in blind-well chambers was compared to that under agarose. Chemotaxis results obtained from both assays for PMNL were similar, however there was a difference in the results for monocyte chemotaxis. PMNL isolated from patients with AIDS, but not ARC, exhibited decreased spontaneous and directed chemotaxis when assessed in blind-well chambers and under agarose. Spontaneous and directed chemotaxis in blind-well chambers of AIDS patients' monocytes was normal. Directed migration of monocytes from ARC patients was greater than that of control, but spontaneous migration was comparable. Under agarose, spontaneous migration was depressed in monocytes of AIDS patients, while migration toward the attractant was depressed in those of ARC patients.

AIDS-Related Complex↗

Hemophilia-associated AIDS in the United States, 1981 to September 1987.

Between January 1, 1981 and September 4, 1987, 407 cases of hemophilia-associated acquired immunodeficiency syndrome (AIDS) had been reported to the Centers for Disease Control. The number of cases diagnosed each year nearly doubled, except in 1986, when cases increased only 50 per cent. Demographic characteristics of the patients did not change over time. The majority (74 per cent) had severe hemophilia and 97 per cent received commercially produced concentrated clotting factors. The cumulative incidence of AIDS between 1981 and September 1987 for persons with severe hemophilia A was substantially greater than that for persons with severe hemophilia B (4.2 cases vs 1.9 cases per 100 persons).

Acquired Immunodeficiency Syndrome↗

Hypergammaglobulinemia associated with human immunodeficiency virus infection.

The serum concentrations of 11 Ig isotypes (IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgA1, IgA2, IgM, IgD, and IgE) were measured in four relatively small groups of homosexual (or bisexual) males. All these patients were seropositive for HIV. Two of the groups (nonprogressors) were clinically stable for approximately 2 years and were characterized either as asymptomatic or with PGL. The third group (progressors) developed AIDS 2-38 months after blood specimens were taken. The fourth group had AIDS. A fifth group of anti-HIV-seronegative heterosexual males completed the study. The geometric mean IgA serum concentration was more markedly elevated over normal control sera than any of the other study groups and was the only Ig isotype that was significantly higher in the progressor than in the nonprogressor group. The geometric IgG1 serum concentration was significantly higher in asymptomatic nonprogressors, PGL-nonprogressors, progressors, and AIDS patient groups than that in HIV-seronegative normals. In contrast, the geometric mean IgG2 serum concentration is depressed in all the anti-HIV-seropositive patients (but not significantly with the AIDS group). Multivariate analysis showed the Ig-isotype assays to have much less predictive power for progression to AIDS than the T-helper cell assays.

Acquired Immunodeficiency Syndrome↗

Human immunodeficiency virus infection in hemophilic children.

The following groups were compared: (1) children less than 18 years old who have hemophilia-associated acquired immunodeficiency syndrome (AIDS) with other children with AIDS and with adults who have hemophilia-associated AIDS and (2) asymptomatic HIV-infected hemophilic children with asymptomatic HIV-infected hemophilic adults. Children with hemophilia-associated AIDS were older than other children with AIDS (medians 13 and 1 years, respectively) and less frequently had lymphocytic interstitial pneumonitis (5% v 48%) but had similar incidences of Pneumocystis carinii pneumonia (51% v 53%) and similar case to fatality ratios (59% v 61%). Children with hemophilia-associated AIDS had P carinii pneumonia significantly less often than did adults with hemophilia-associated AIDS, but both had similar case to fatality ratios (adults 72% with P carinii pneumonia, 68% dead). Significantly more hemophilic children than adults with AIDS were nonwhite (30% v 14%) and resided in the tristate area of New York/New Jersey/Pennsylvania (43% v 25%). The immune effects of human immunodeficiency virus (HIV) to date on asymptomatic pediatric and adult hemophiliacs are similar but may be more severe in adults. It is concluded that, although some of the clinical manifestations of AIDS (eg, lymphocytic interstitial pneumonitis) occurring or not occurring in older children infected through blood factor products differ from those of other children with AIDS, disease outcome to date is equally poor. The reasons for the differences between hemophilic children and hemophilic adults with and without AIDS warrant further investigation.

Acquired Immunodeficiency Syndrome↗

Hemophiliac patient's knowledge and educational needs concerning acquired immunodeficiency syndrome.

The Patient Knowledge Assessment Study (PKAS) was conducted among 107 male hemophilic patients, aged 15 to 67 years, at 19 hemophilia treatment centers (HTC). Participants were given a 30-item questionnaire concerning the cause of acquired immunodeficiency syndrome (AIDS), the groups at risk, and modes of transmission. The questionnaire included questions on the participant's status in regard to antibody to human T-lymphotropic retrovirus, type III/lymphadenopathy-associated virus (HTLV-III/LAV), and the meaning of this test result. HTC health-care providers were asked to complete a separate questionnaire containing 17 questions about information given patients concerning their HTLV-III/LAV antibody status and its meaning. Overall, patients had a good base of knowledge about AIDS; however, there were gaps in this knowledge. Twenty-nine percent of patients did not know that spouses of AIDS patients were at risk for AIDS; 47% did not know that sexual partners of persons with hemophilia were at risk; and 32% did not know that hemophilic children were at risk. Further, only 69% understood that antibody-positive individuals had had contact with the AIDS virus. Identifying these and other areas of misunderstanding will provide the information needed to design educational strategies and psychosocial support programs appropriate for the hemophilic population, and which may serve as a model for other populations.

Acquired Immunodeficiency Syndrome↗

An outbreak of necrotizing enterocolitis. Association with transfusions of packed red blood cells.

Of 187 newborns admitted to a 33-bed, level III neonatal intensive care unit between January 1, 1985 and June 23, 1985, 33 developed necrotizing enterocolitis during their hospital stay. Twenty of the 33 newborns (61%) had onset of symptoms between April 1 and June 23, suggesting clustering during this period. A case-control study, with matching on birth weight class, approximate date of admission to the unit and approximate duration of stay, failed to reveal any association of the syndrome with type or timing of feeding, perinatal hypoxic events, as determined by apgar scores and labor history, or specific microbial organisms. By contrast, however, transfusion of packed red blood cells was highly and significantly associated with the syndrome (odds ratio = 15.1, 95% confidence interval = 2.59-92.51). In addition, therapy with caffeine, with theophylline, and with furosemide were moderately associated with the syndrome, although not significantly so. During this outbreak period, the incidence of necrotizing enterocolitis by birth weight was 30.6% in infants less than 1,500 gm, 10.8% in infants 1,500-2,500 gm, and 11.9% in infants 2,500 gm or more. These findings confirm the importance of low birth weight as a risk factor for development of the syndrome and suggest that insults to volume homeostasis, such as transfusion and use of diuretics, need to be considered as possible mechanisms whereby necrotizing enterocolitis is initiated.

Birth Weight↗

Micromethod for assaying reverse transcriptase of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus.

A micromethod for assaying the reverse transcriptase enzyme of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus in cocultures of clinical specimens for viral isolation was developed and compared with the macromethod in use. Ultracentrifuged, pelleted, and solubilized viral culture supernatants were transferred into either tubes (macromethod) or microtiter plates (micromethod) and incubated with tritiated enzyme substrate. Trichloroacetic acid-precipitated DNA was collected on individual filter papers with a Millipore filtration manifold (macromethod) or on filter sheets using a semiautomated cell harvester (micromethod). Filters were then placed in scintillation fluid and counted on a beta scintillation counter. Results of the micromethod significantly correlated to those of the macromethod, with a linear relationship between the two. The cutoffs for positivity based on the mean + 2 standard deviations for a set of known negative specimens (n = 19) was 4,973 cpm for the micromethod compared with 5,336 for the macromethod. The intrarun and interrun variations were comparable for both methods. There was a 67% increase in the maximal daily number of specimens which could be run (100 versus 60) as well as a reduction in reagent use. In summary, the micromethod utilizing a semiautomated cell harvester is comparable to the existing macromethod in accuracy and is an improvement due to savings in time and reagents.

HIV↗

Risk factors for Guillain-Barré syndrome.

In 100 cases of Guillain-Barré syndrome (GBS) reported from 10 metropolitan areas to the Centers for Disease Control (CDC) after the 1976-77 influenza vaccination campaign and matched associate or spouse controls, we searched for risk factors for GBS other than A/New Jersey/1976 influenza vaccination and acute respiratory infection. The 47 vaccinated cases recalled influenza vaccination in past years less frequently than did controls (p less than 0.025). Cases and controls did not differ in the number of previous vaccinations or in interval from last vaccination. Cases also gave a history of allergy less frequently than controls. There were no other significant differences.

Epidemiologic Methods↗

Effects of exposure to factor concentrates containing donations from identified AIDS patients. A matched cohort study.

We compared recipients of eight lots of factors VIII and IX voluntarily withdrawn from distribution because one donor was known to have subsequently developed the acquired immunodeficiency syndrome with a nonexposed cohort matched by age, sex, and factor use. The factor VIII recipient cohorts did not differ in prevalence of antibody to human immunodeficiency virus (HIV) (exposed, 75%; nonexposed, 86%), T-cell subset numbers (median: exposed, 619 T-helper cells per cubic millimeter; nonexposed, 659 T-helper cells per cubic millimeter), T-helper to T-suppressor ratios, or immunoglobulin levels. Exposed individuals had higher levels of immune complexes by C1q binding and staphylococcal binding assays and lower responses to phytohemagglutinin and concanavalin A. However, only the staphylococcal binding assay values were outside the normal range for our laboratory. Factor IX recipient cohorts did not differ in HIV antibody prevalence (exposed, 30%; nonexposed, 40%) or any immune tests. Although exposed and nonexposed individuals did not differ from each other in a clinically meaningful fashion at initial testing, both the exposed and nonexposed cohorts had high rates of HIV seroprevalence. Market withdrawals were clearly insufficient means of limiting the spread of HIV in hemophilic patients; however, the currently available methods of donor screening and viral inactivation of blood products will prevent continued exposure within this population.

Acquired Immunodeficiency Syndrome↗

The role of parvovirus B19 in aplastic crisis and erythema infectiosum (fifth disease).

In 1984, simultaneous outbreaks of aplastic crisis and erythema infectiosum occurred in northeastern Ohio. Sera were analyzed from 26 patients with aplastic crisis: 24 had IgM specific for parvovirus B19, five had B19-like particles by electron microscopy, and 13 had DNA from B19; no sera from 33 controls had evidence of recent infection with B19 (P less than .0001). DNA from B19 was also detected in specimens of throat gargle and urine from two patients with aplastic crisis. Sera from 36 of 51 children with erythema infectiosum had B19-specific IgM, compared with serum from one of 42 susceptible controls (P less than .0001). DNA from B19 was detected in sera from only two of 51 patients who had erythema infectiosum. The secondary attack rates among susceptible contacts decreased with age (overall total, 49.6%). Differential rates of asymptomatic infection were observed among black (68.8%) and white (20.0%) household members (P = .003). These were the first identified simultaneous outbreaks of aplastic crisis and erythema infectiosum. Their occurrence provided an opportunity to study the epidemiology and spectrum of B19 infection with geographically and temporally matched comparison groups; our results support the hypothesis that infection with parvovirus causes these two clinical entities.

Adolescent↗

Human T-lymphotropic retrovirus type III/lymphadenopathy-associated virus antibody. Association with hemophiliacs' immune status and blood component usage.

We studied the human T-lymphotropic retrovirus type III/lymphadenopathy-associated virus (HTLV-III/LAV) antibody status of 234 factor VIII concentrate recipients, 36 factor IX concentrate recipients, 69 long-term recipients of frozen packed red blood cells, and 47 persons not receiving routine transfusion therapy. Factor VIII concentrate recipients had a significantly higher rate of seropositivity (74%) than any other group. Factor IX concentrate recipients had a significantly higher rate (39%) than recipients of frozen packed red blood cells (4%) or nontransfused persons (4%). In factor VIII concentrate recipients, HTLV-III/LAV seropositivity was significantly associated with more severe hemophilia, greater factor dosage, elevated immunoglobulin and immune complex levels, lower T-helper lymphocyte numbers, and lower ratios of T-helper to T-suppressor lymphocytes. For factor IX concentrate recipients, seropositivity was associated with more severe hemophilia. Antibody-positive factor IX concentrate recipients had a lower rate of seropositivity to HTLV-III/LAV p41 membrane antigen than did antibody-positive factor VIII concentrate recipients, but factor VIII and factor IX concentrate recipients had similar rates of seropositivity to core antigens. We conclude that both factor VIII and factor IX concentrates may transmit HTLV-III/LAV. For factor VIII recipients, HTLV-III/LAV seropositivity is associated with altered immune test results.

Adolescent↗

Immune status of blood product recipients.

Persons with hemophilia are at risk of the acquired immunodeficiency syndrome (AIDS), and clinically asymptomatic hemophiliacs have shown a high incidence of AIDS-like immune abnormalities, facts leading to speculation that many hemophiliacs have been exposed to the AIDS agent through their blood products. We therefore evaluated the immune status of three groups of blood product recipients without AIDS in New York City, including 47 persons with hemophilia A receiving factor VIII concentrate, 50 persons with homozygous beta-thalassemia, and 27 persons with sickle cell anemia receiving frozen-packed RBCs and 20 healthy persons who had not received a transfusion. Hemophiliac participants had significantly lower lymphocyte counts (median, 1,826/cu mm) than did the thalassemic (6,110/cu mm) or anemic (4,443/cu mm) participants, had lower numbers of T-helper lymphocytes (median, 533 cells/cu mm v 1,733 cells/cu mm and 1,554 cells/cu mm), and had a lower T-helper/suppressor ratio (median, 0.8 v 1.8 and 2.1). These differences remained after adjustment for age and sex. Thus, AIDS-like immune abnormalities were found in patients receiving factor concentrate, but not in those receiving RBCs. These defects could be due to both an immunosuppressive effect of the lyophilized factor itself and to contact with the AIDS agent.

Acquired Immunodeficiency Syndrome↗

Immune complexes in the acquired immunodeficiency syndrome (AIDS): relationship to disease manifestation, risk group, and immunologic defect.

Immune complex assays (and other immunologic tests) were performed on sera from 162 patients with the acquired immunodeficiency syndrome (AIDS) and 275 AIDS-related subjects. Immune complexes were detected in 89% of AIDS patients and 93% of homosexual men with lymphadenopathy. Immune complex levels in AIDS patients were not associated with a particular risk group or with types of opportunistic infection or malignancy; however, they correlated with other laboratory features of the immune defect (depression in T helper cells and T helper/suppressor-cell ratio, and IgG levels). Immune complexes were also detected in a lesser proportion of risk-group controls (homosexual men, hemophiliacs, Haitians). In risk-group controls, immune complex levels were associated with certain features reflecting sexual practice, blood product exposure, or infection, but these features did not account for the higher levels found in AIDS patients. In appropriate situations, immune complex assays may be of value as screening tests or, possibly, as prognostic indicators for AIDS or AIDS-related syndromes.

Acquired Immunodeficiency Syndrome↗

A longitudinal study of patients with hemophilia: immunologic correlates of infection with HTLV-III/LAV and other viruses.

A comprehensive study was initiated to examine the immunologic status of a sample (n = 47) of the asymptomatic hemophilia A and B populations of metropolitan Atlanta and to determine if any of the abnormalities changed with time or correlated with infection by human T cell leukemia virus type III and lymphadenopathy-associated virus (HTLV-III/LAV) or other viruses either alone or in combination. Patients with hemophilia A (Hem-A) showed a defect in cellular immunity evidenced by a depressed T cell helper/suppressor ratio (P less than .0001), an increased absolute T suppressor cell number (P less than .0001), and a diminished number of T helper cells (P = .003) when compared with health professionals. Lymphocytes from these patients also showed a reduced ability to transform in response to phytohemagglutinin and pokeweed mitogen. No deterioration in immune status was seen during a median ten-month period of follow-up. Sixty-four percent of Hem-A patients had antibodies to HTLV-III/LAV and those who were seropositive had a significantly decreased helper/suppressor cell ratio (P = .018) and a diminished T helper cell number (P = .002); they were also more likely to have had exposure to cytomegalovirus than HTLV-III/LAV-negative Hem-A patients (P = .016). Heavy use of factor VIII concentrate was associated with a decreased number of T helper cells (P = .037) and seropositivity for HTLV-III/LAV (P = .011 in 1982). Hemophilia patients had higher IgG, immune complex, and beta 2-microglobulin levels than health professionals (P less than .0001). Although the most prominent abnormality observed in T cell subsets of patients with hemophilia is an increase in T suppressor cells, a finding likely to be associated with immune augmentation in response to multiple stimuli, the T cell abnormality that was predictive of exposure to HTLV-III/LAV, the putative acquired immunodeficiency syndrome agent, was a diminished number of T helper cells.

Adult↗